Diabetic Nephropathy

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What is diabetic nephropathy?

Diabetic nephropathy is a complication of diabetes that is caused by uncontrolled high blood sugar. High blood sugar damages the filtering system of the kidneys (nephron ). Over time, the damage can lead to kidney failure. Diabetic nephropathy is the most common cause of kidney failure in the United States.¹

Preventing or slowing kidney damage is most important in managing this disease. Keeping blood sugar and blood pressure as near to normal as possible and eating a healthy diet can reduce your risk of developing this condition or progressing to kidney failure.

What causes diabetic nephropathy?

Persistently high blood sugar levels caused by diabetes can, over time, damage the blood vessels in your kidneys, resulting in diabetic nephropathy.

What are the symptoms?

There are no symptoms in the early stages of diabetic nephropathy. A small amount of protein in the urine (microalbuminuria) is the first sign of kidney damage. As damage to the kidneys progresses, larger amounts of protein spill into the urine (macroalbuminuria) and blood pressure rises. Your cholesterol and triglyceride levels will increase as well. As kidney function declines, you may notice swelling in your body, at first in your feet and legs.

Regular checkups with your health professional are important to detect early signs of diabetic nephropathy and begin efforts to prevent further kidney damage.

What increases my risk for diabetic nephropathy?

For reasons doctors don't yet understand, only some people with diabetes develop nephropathy. Diabetic nephropathy eventually occurs in up to 40% of people who have diabetes.²

If you have both diabetes and high blood pressure, you have an even greater risk of developing nephropathy. Other risk factors for the disease include smoking and a high cholesterol level. In addition, people of Native American, African-American, or Hispanic (especially Mexican-American) descent have a greater-than-average risk.¹

How is it diagnosed?

As the kidney becomes less able to filter wastes, proteins from the blood spill into the urine. One protein, albumin, helps control the fluid balance in the body. Early in diabetic nephropathy, before other symptoms are present, the kidneys are still able to filter waste and function normally. The only sign of kidney disease may be an increase in albumin in the urine. Urine tests for albumin can detect early kidney disease.

Microalbumin urine tests can detect very small amounts of protein in the urine that cannot be detected by a routine urine test, allowing early detection of nephropathy. Early detection is important to prevent further damage to the kidneys. Yearly urine tests for protein are recommended for all people with diabetes.

• If you have type 1 diabetes, you should have a microalbumin test every year after you have had diabetes for 5 years.
• If your child has diabetes, yearly testing should begin at puberty.
• If you have type 2 diabetes, you should begin yearly testing at the time you are diagnosed with diabetes.

How can it be prevented?

Diabetic nephropathy can be prevented or its progress slowed by carefully keeping your blood sugar levels as close to normal as possible. You can do this by maintaining a healthy weight, taking your medications as prescribed, checking your blood sugar level frequently, and exercising regularly. At the first sign of too much protein in your urine, there are high blood pressure medications that you can take to slow the progression of nephropathy.

How is it treated?

Medications that lower blood pressure and prevent or slow the development of diabetic nephropathy are recommended for all people who have diabetes and have a high risk for nephropathy. Examples of these medications are angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). You may need to take more than one medication, especially if you also have high blood pressure. Treatment to control blood pressure and blood sugar levels can reduce kidney failure caused by diabetes by 50%.³

Other steps you can take include the following:

• Work with your health professional to keep your blood pressure below 130/80 millimeters of mercury (mm Hg). This blood pressure level is recommended by the American Diabetes Association. The level recommended by other organizations may vary. Talk with your doctor about what your target blood pressure level should be.
• Work with your health professional to keep your cholesterol level as close to normal as possible. You may need to take medications to help lower your cholesterol.
• Eat a low-fat diet and exercise regularly to maintain a healthy weight. People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease). Talk to your health professional about a referral to a dietitian. A dietitian can help you choose foods that are low in fat and help you reach your goals.⁴
• Eat a moderate amount of protein to reduce the stress on your kidneys. Most doctors recommend that protein make up no more than 10% of your daily calories.
• Limit the amount of salt in your diet to prevent high blood pressure from becoming worse (if your blood pressure is affected by salt).
• Do not smoke or use other tobacco products.

Frequently Asked Questions

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There are no symptoms in the early stages of diabetic nephropathy. The only sign of kidney damage may be small amounts of protein leaking into the urine (microalbuminuria). Normally, protein is not found in urine except during periods of high fever, strenuous exercise, pregnancy, or infection.

In people with type 1 diabetes, diabetic nephropathy usually develops 5 to 10 years after the onset of diabetes. People with type 2 diabetes may find out that they already have a small amount of protein in the urine (microalbuminuria) at the time diabetes is diagnosed because they may have had diabetes for several years.

As diabetic nephropathy progresses, you may have:

• Swelling (edema), first in the feet and legs and later throughout your body.
• A rise in blood pressure.
• Large amounts of protein leaking into your urine (macroalbuminuria, also known as overt nephropathy).
• Increasing cholesterol and triglyceride levels.

Once the kidneys are severely damaged, blood sugar levels may drop because the kidneys cannot remove excess insulin or filter oral medications that increase insulin production, such as glipizide (Glucotrol) or glyburide (for example, Micronase).

Other symptoms may occur as nephropathy worsens. See the topic Chronic Kidney Disease for more information.

Diabetic nephropathy is diagnosed using tests that check for a protein (albumin) in the urine, which is an indicator of kidney damage. Your urine will be checked for protein (urinalysis) when you are diagnosed with diabetes.

Microalbumin urine tests can detect very small amounts of protein in the urine that cannot be detected by a routine urine test, allowing early detection of nephropathy. Early detection is important to prevent further damage to the kidneys. The results of two tests done within a 3- to 6-month period are needed to diagnose nephropathy.

When to begin checking for protein in the urine depends on the type of diabetes you have. Once testing begins, it should be done every year.²

A microalbuminuria dipstick test is a simple test that can detect small amounts of protein in the urine (microalbuminuria, also called proteinuria). The strip changes color if protein is present, providing an estimate of the amount of protein. A spot urine test for microalbuminuria is a more precise laboratory test that can measure the exact amount of protein in a urine sample. Either of these tests may be used to test your urine for protein.

If your health professional suspects that the protein in your urine may be caused by a disease other than diabetes, a small sample of kidney tissue may be removed and examined (renal biopsy).⁵

Other tests

It is important to check your blood pressure regularly, both at home and in your health professional's office, because blood pressure rises as kidney damage progresses. About one-third of people with type 2 diabetes have high blood pressure at the time diabetes is diagnosed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).² The level recommended by other organizations may vary. Talk with your health professional about what your target blood pressure level should be. Keeping your blood pressure at or below this target can prevent or slow kidney damage.

Blood levels of cholesterol and triglycerides also should be checked regularly to see whether diabetes, nephrotic syndrome, or other factors are raising your blood cholesterol level. High cholesterol can increase the risk of hardening of the arteries (atherosclerosis), possibly leading to heart disease, peripheral arterial disease, and stroke.

Diabetic nephropathy is treated with medications that lower blood pressure and protect the kidneys. These medications may reverse kidney damage and are started as soon as any amount of protein is found in the urine (microalbuminuria). The use of these medications before nephropathy occurs also may help prevent nephropathy in people who have normal blood pressure.^{6, 7}

If you have high blood pressure, two or more medications may be needed to lower your blood pressure enough to protect the kidneys. Medications are added one at a time as needed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).² The level recommended by other organizations may vary. Talk with your doctor about what your target blood pressure level should be. For more information on blood pressure medications, see the topic High Blood Pressure (Hypertension).

It is also important to keep your blood sugar as close to normal as possible. Maintaining blood sugar levels at a close to normal level prevents damage to the small blood vessels in the kidneys.

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You may also want to restrict the amount of protein in your diet. Most health professionals recommend that protein make up no more than 10% of your daily calories. Talk with a dietitian if you need help balancing your diet.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Using low-dose aspirin therapy and eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁴

Initial treatment

Medications that are used to treat diabetic nephropathy are also used to control blood pressure. If you have a very small amount of protein in your urine, these medications may reverse the kidney damage. Medications used for initial treatment of diabetic nephropathy include:

• Angiotensin-converting enzyme (ACE) inhibitors, such as captopril, lisinopril, ramipril, and enalapril. ACE inhibitors have been shown to protect kidney function in people with type 1 diabetes, even in those who do not have high blood pressure.⁸ In addition, they may reduce your risk of heart and blood vessel (cardiovascular) disease. One study found that ramipril cut the risk of cardiovascular disease in people with diabetes (type 1 and type 2 diabetes) by 25% to 30%.⁹
• Angiotensin II receptor blockers (ARBs), such as candesartan cilexetil, irbesartan, losartan potassium, and telmisartan. You may be given both an ACE inhibitor and an ARB. The combination of these medications may provide greater protection for your kidneys than either medication alone.

If you also have high blood pressure, two or more medications may be needed to lower your blood pressure enough to protect your kidneys. Medications are added one at a time as needed. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).²

It is also important to maintain your blood sugar as close to normal as possible to prevent damage to the small blood vessels in the kidneys. The American Diabetes Association recommends that you keep your blood sugar levels at:²

• 80 milligrams per deciliter (mg/dL) to 120 mg/dL before meals and 100 mg/dL to 140 mg/dL at bedtime when using a blood sample drawn from a vein (a whole-blood sample).
• 90 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime when using a blood sample drawn from a fingertip (plasma blood sample).
• Less than 180 mg/dL 1 to 2 hours after meals.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁴

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You will also want to restrict the amount of protein in your diet. Most doctors recommend that protein make up no more than 10% of your daily calories. Talk with a dietitian if you need help balancing your diet.

Ongoing treatment

As diabetic nephropathy progresses, blood pressure usually rises, making it necessary to add additional medications to control blood pressure. The goal set by the American Diabetes Association is to keep your blood pressure less than 130/80 mm Hg, if possible, to protect your kidneys. The level recommended by other organizations may vary. Talk with your health professional about what your target blood pressure level should be.

Your health professional may recommend that you take the following medications. You may need to take different combinations of these medications to best control your blood pressure. Medications include:

• A combination of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). A combination of these medications may be more effective in controlling blood pressure than either used alone.
• Calcium channel blockers, such as amlodipine (Norvasc, for example), diltiazem (Cardizem SR, Dilacor XR, or Tiazac, for example), nifedipine (Adalat or Procardia XL, for example), and verapamil (Calan SR or Isoptin SR, for example).
• Diuretics. Medications such as bumetanide, chlorthalidone, and hydrochlorothiazide help lower blood pressure by removing sodium and water from the body.

It is also important to maintain your blood sugar as close to normal as possible to prevent damage to the small blood vessels in the kidneys. The American Diabetes Association recommends that you keep your blood sugar levels at:²

• 80 mg/dL to 120 mg/dL before meals and 100 mg/dL to 140 mg/dL at bedtime when using a blood sample drawn from a vein (a whole-blood sample).
• 90 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime when using a blood sample drawn from a fingertip (plasma blood sample).
• Less than 180 mg/dL 1 to 2 hours after meals.

People with diabetes are 2 to 4 times more likely than people who don't have diabetes to die of heart and blood vessel diseases. Eating a low-fat diet can help prevent heart attack, stroke, and other large blood vessel disease (macrovascular disease).⁴

Limiting the amount of salt in your diet can help keep your high blood pressure from becoming worse. You will also want to restrict the amount of protein in your diet. Most doctors recommend that protein make up no more than 10% of your daily calories. Ask to speak with a dietitian if you need help balancing your diet.

People who have diabetic nephropathy also have an increased risk of illness and death from cardiovascular disease, so it is important to work with your health professional to lower your risk of heart problems. Strategies include keeping your cholesterol at a normal level, using low-dose aspirin therapy, getting regular exercise, and not smoking.

Treatment if the condition gets worse

If damage to the blood vessels in the kidneys continues, kidney failure eventually develops. Once that occurs, it is likely that you will need dialysis treatment (renal replacement therapy), which is an artificial method of filtering the blood, or a kidney transplant to survive. For more information, see the topic Chronic Kidney Disease.

What to think about

Diabetic nephropathy can get worse during pregnancy and can affect the growth and development of the fetus. If your nephropathy is not severe, your kidney function may return to its prepregnancy level after the baby is born. If you have severe nephropathy, pregnancy may lead to permanent worsening of your kidney function.¹⁰

If you have nephropathy and are pregnant or planning to become pregnant, talk with your health professional about which medications you can take. You may not be able to take some medications (for example, angiotensin-converting enzyme [ACE] inhibitors, such as captopril, lisinopril, ramipril, or enalapril) during pregnancy because they may harm your developing baby. Talk to your health professional about your medications and your desire to become pregnant.

Prevention

Prevention is the best way to avoid kidney damage from diabetic nephropathy.

• Keep your blood glucose levels as close to normal as possible. Keeping your blood sugar within a safe range by eating a balanced diet, taking your medications (insulin or oral medications), and getting regular exercise may help you prevent diabetic nephropathy. The American Diabetes Association recommends that you keep your blood sugar levels at:²
  • 80 mg/dL to 120 mg/dL before meals and 100 mg/dL to 140 mg/dL at bedtime when using a blood sample drawn from a vein (a whole-blood sample).
  • 90 mg/dL to 130 mg/dL before meals and 110 mg/dL to 150 mg/dL at bedtime when using a blood sample drawn from a fingertip (plasma blood sample).
  • Less than 180 mg/dL 1 to 2 hours after meals.
  Your health professional will want you to check your blood sugar several times each day. For more information, see:

  Home blood sugar monitoring.

• Have yearly testing for protein in your urine.
  • If you have type 1 diabetes, begin urine tests for protein after you have had diabetes for 5 years.
  • Children with type 1 diabetes should begin yearly screening for urine protein beginning at puberty.
  • If you have type 2 diabetes, begin screening at the time diabetes is diagnosed.
• Maintain blood pressure at less than 130/80 mm Hg with medication, diet, and exercise.¹¹ Learn to check your blood pressure at home. For more information, see:

  Monitoring your blood pressure at home.

• Maintain a healthy weight. This can help you prevent other diseases, such as high blood pressure and heart disease. For more information, see the topic Healthy Weight.
• Follow the nutrition guidelines for hypertension (including the Dietary Approaches to Stop Hypertension, or DASH, diet). For more information, see:

  Tips for following the Dietary Approaches to Stop Hypertension (DASH) diet.

• Do not smoke or use other tobacco products. For more information, see the topic Quitting Tobacco Use.

If you already have diabetic nephropathy, you may be able to slow the progression of kidney damage by:

• Avoiding dehydration by promptly treating other conditions, such as diarrhea, vomiting, or fever, that can cause it. Be especially careful during hot weather or when you exercise.
• Reducing your risk of heart disease. Lifestyle changes such as eating a low-fat diet, quitting smoking, and getting regular exercise can help reduce your overall risk of developing heart disease and stroke. For more information, see the topic Coronary Artery Disease.
• Treating other conditions that may block the normal flow of urine out of the kidneys, such as kidney stones, an enlarged prostate, or bladder problems.
• Avoiding the use of medications that may be harmful to your kidneys. Be sure that your health professional knows about all prescription, nonprescription, and herbal medicines you are taking.
• Avoiding X-ray tests that require IV contrast material, such as angiograms, intravenous pyelography (IVP), and some CT scans. IV contrast can cause further kidney damage. If you do need to have these types of tests, make sure your health professional knows that you have diabetic nephropathy.
• Avoiding situations where you risk losing large amounts of blood, such as unnecessary surgeries. Do not donate blood or plasma.
• Limiting alcohol to 1 drink per day for women and older adults and 2 drinks per day for men.

If you have diabetes, you can reduce the chances of developing nephropathy, or slow the disease if you already have it, by working with your health professional to keep your blood sugar levels within a safe range.² Your health professional will want you to check your blood sugar several times each day. For more information, see:

Home blood sugar monitoring.

Other steps you can take include the following:

• Check your blood pressure often and also have it checked at your health professional's office. The American Diabetes Association recommends a target blood pressure of less than 130/80 millimeters of mercury (mm Hg).² The level recommended by other organizations may vary. Talk with your health professional about the target blood pressure that is right for you. Learn to check your blood pressure at home. For more information, see:

  Monitoring your blood pressure at home.

• Be sure to take your blood pressure medications as prescribed.
• Follow the nutrition guidelines for hypertension (including the Dietary Approaches to Stop Hypertension, or DASH, diet). For more information, see:

  Tips for following the Dietary Approaches to Stop Hypertension (DASH) diet.

• Maintain a healthy weight for your height and age by eating a well-balanced diet and exercising regularly. A low-fat diet and regular exercise also will lower your risk of heart and blood vessel (cardiovascular) disease. See the body mass index (BMI) chart for adults or the same chart in metric to determine your healthy weight. For children (2 to 20 years old), see calculating body mass index (BMI) in children to determine your child's healthy weight.
• Do not smoke or use other tobacco products. People with diabetes who smoke raise their risk of nephropathy, cardiovascular disease, and other complications of diabetes.
• Eat a moderate amount of protein. If you have nephropathy, your health professional may recommend limiting protein. Experts debate the value of cutting back on protein in the diet. For now, most health professionals recommend that protein make up no more than 10% of daily calories.
• Limit salt. Your health professional may recommend that you cut back on salt because it may make high blood pressure worse.

What to think about

If your diabetic nephropathy becomes worse and kidney failure develops, you may need to follow a specific diet. A dietitian can help you understand the requirements of this diet and help you make healthy choices.

Organizations

• Chronic Kidney Disease
• Diabetic Neuropathy
• Diabetic Retinopathy
• High Blood Pressure (Hypertension)
• Nephrotic Syndrome
• Type 1 Diabetes
• Type 2 Diabetes: Living With Complications
• Type 2 Diabetes: Living With the Disease

Citations

1. American Diabetes Association (2004). Nephropathy in diabetes. Clinical Practice Recommendations 2004. Diabetes Care, 27(Suppl 1): S79–S83.

2. American Diabetes Association (2006). Standards of medical care in diabetes. Clinical Practice Recommendations 2005. Diabetes Care, 29(Suppl 1): S3–S42.

3. Diabetes: Disabling, Deadly, and on the Rise (2002). At a Glance Series. Atlanta: Centers for Disease Control and Prevention.

4. Van Dam RM, et al. (2002). Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Annals of Internal Medicine, 136(3): 201–209.

5. Steele AW (2001). Kidney disease. In HC Gerstein, RB Haynes, eds., Evidence-Based Diabetes Care, pp. 429–465. Hamilton, ON: BC Decker.

6. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group (2001). Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). Journal of Pediatrics, 139(6): 804–812.

7. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002). Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA, 287(19): 2563–2569.

8. ACE Inhibitors in Diabetic Nephropathy Trialist Group (2001). Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? Annals of Internal Medicine, 134(5): 370–379.

9. Gerstein HC, et al. (2000). Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Lancet, 355(9200): 253–259.

10. American Diabetes Association (2004). Preconception care of women with diabetes. Clinical Practice Recommendations 2004. Diabetes Care, 27(Suppl 1): S76–S78.

11. Cohen EP (2001). Chronic renal failure and dialysis. In DC Dale, DD Federman, eds., Scientific American Medicine, section 11, chap. 1. New York: WebMD.

Other Works Consulted

• Bakris GL (2003). The evolution of treatment guidelines for diabetic nephropathy. Postgraduate Medicine, 113(5): 35–50.

Author:	Sydney Youngerman-Cole, RN, BSN, RNC	Last Updated January 20, 2005
Medical Review:	Caroline S. Rhoads, MD - Internal Medicine D C Mendelssohn, MD, FRCPC - Nephrology
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